This ShEEP application requested fund to purchase a Acquity UPLC Xevo TQ-XS LCMS Mass Spectrometer that will be used to support VA research at the Hunter Holmes McGuire Medical Center. Five major VA-funded investigators including Drs. Zhou, Pandak, Hylemon, Bajaj and Ren require this equipment to measure bile acids, oxysterols and lipids for their funded VA Merit Awards and NIH grants. Currently, no LC/MC is available at McGuire VA Medical Center. The Xevo TQ-XS is an advanced benchtop tandem quadrupole mass spectrometer which expands the scope of ultimate sensitivity analysis in the complex matricies encountered in biomedical research programs . This equipment supports biomedical research that requires intimate knowledge of key biochemicals related to disease pathways. A major aspect of this research involves accurate, reproducible measurements of such biochemicals at low levels in biological samples. The Acquity UPLC Xevo TQ-XS LCMS Mass Spectrometer was specifically designed to provide these types of quality measurements in support of such research. The Acquity UPLC Xevo TQ-XS LCMS Mass Spectrometer features StepWave XS? ion transfer optics delivering enhanced sensitivity, robustness, and reliability; passively removing gas load and undesirable neutral contaminants while actively transferring ions into the mass analyzer. Sensitivity benefits are more accessible as the Xevo TQ-XS also features a tool-free probe design which allows users much easier maintenance, optimization and improved reproducibility between operators. Method transfer onto the Xevo TQ-XS is made simple by the Xtended Dynamic Range (XDR?) detector which allows six orders of linear dynamic range. When combined these advances allow new levels of reproducible and accurate quantitation of analytes at the lowest concentrations. The 2D Technology functions for Trapping, Heart Cutting, Parallel Column Regeneration, At-Column Dilution, Time de-coupled chromatography and 2D Comprehensive chromatography which further enhance the analytical separation capability of the iClass UPLC LC system Xevo TQ XS system providing the versatility needed to address the complexity in biological sample LCMSMS analysis. Combining these two bioanalytically appropriate technologies provides the instrumental capabilities required for successful completion of these funded studies related to metabolic liver diseases that are target areas of the VA research mission.